9626
Y. Koriyama et al. / Tetrahedron 58 (2002) 9621–9628
1H NMR (270 MHz, CDCl3) d 0.96 (t, 3H, J¼7.3 Hz), 1.26
(t, 3H, J¼6.9 Hz), 1.45–2.04 (m, 4H), 2.38 (s, 3H), 3.66–
3.78 (m, 1H), 4.01–4.12 (m, 1H), 4.25 (dd, 1H, J¼4.8,
10.1 Hz), 5.59–5.75 (m, 1H), 6.69 (dd, 1H, J¼4.5,
10.4 Hz), 7.23 (d, 2H, J¼8.1 Hz), 7.54 (d, 2H, J¼8.1 Hz);
be obtained, and therefore, this material was used for the
next step without further characterization.
5.4.5. 2-Ethoxy-6-propyl-1-(toluene-4-sulfonyl)-piper-
idine (12). A mixture of tributyltin hydride (0.34 mmol),
AIBN (cat. amt.), and dithiocarbonic acid O-[6-ethoxy-2-
propyl-1-(toluene-4-sulfonyl)piperidin-3-yl]ester S-methyl
ester (45 mg, 0.1 mmol) in toluene (3 mL) was refluxed
for 5 h. After cooling to 08C, the reaction was quenched by
an addition of sat. NaCl aq, extracted with AcOEt, dried
over Na2SO4, and then evaporated in vacuo. The crude
product was purified on preparative silica gel TLC (pre-
treated with phosphate buffer, hexane–ether¼12:1, multiple
development) to give the title compound as a white
crystalline solid. Yield 12.9 mg (0.04 mmol, 38%).
IR (CHCl3) 2950, 1680, 1340, 1170, 1020, 580 cm21
;
[a]2D3¼þ39.2 (c 0.59, EtOH); MS (exact mass calcd for
C22H35NO2S–OEt, m/e 292.1007, found m/e 292.1035).
5.4.3. 6-Ethoxy-2-propyl-1-(toluene-4-sulfonyl)-piper-
idin-3-ol (11). To a solution of 6-ethoxy-2-propyl-1-
(toluene-4-sulfonyl)-1,6-dihydro-2H-pyridin-3-one (610 mg,
1.8 mmol) in 25 mL of MeOH was added NaBH4, keeping
the temperature below 2308C. The reaction was monitored
by TLC. After the starting material was consumed, the
reaction was quenched by an addition of acetone (12.2 mL).
The solvent was removed under reduced pressure, and to the
residue was added AcOEt. The whole was washed with sat.
NaCl aq, dried over Na2SO4, and then concentrated in
vacuo. The crude product was purified by silica gel
column chromatography (hexane–ether¼1:1) to give a
mixture of saturated and unsaturated alcohols (570 mg). The
mixture was hydrogenated for 27 h under an atmosphere
(balloon) of hydrogen in EtOH in the presence of 10% Pd/C
(73 mg). After filtration through a celitew pad, the crude
product was purified by silica gel column chromatography
(hexane–ether¼1:1) to give the title compound as a
colorless crystalline. Yield 564.7 mg (1.65 mmol, 92%, 2
steps).
1H NMR (270 MHz, CDCl3) d 0.92 (t, 3H, J¼7.3 Hz), 1.20
(t, 3H, J¼7.1 Hz), 1.24–1.91 (m, 10H), 2.42 (s, 3H), 3.47–
3.59 (m, 1H), 3.71–3.87 (m, 2H), 5.23 (d, 2H, J¼2.3 Hz),
7.29 (d, 2H, J¼8.1 Hz), 7.70 (d, 2H, J¼8.1 Hz); IR (CHCl3)
2950, 1340, 1160, 920, 750, 660 cm21; MS (exact mass
calcd for C17H27NO3S, m/e 325.1712, found m/e 325.2100).
5.4.6. 2-Allyl-6-propyl-1-(toluene-4-sulfonyl)piperidine.
To a solution of 2-ethoxy-6-propyl-1-(toluene-4-sulfonyl)-
piperidine (250 mg, 0.76 mmol) in CH2Cl2 (20 mL) was
added
a
solution of allyltrimethylsilane (183 mg,
1.61 mmol) in CH2Cl2 (15 mL), and the mixture was cooled
to 2788C. To the resulting mixture was added a solution of
BF3·OEt2 (229 mg, 1.61 mmol) in CH2Cl2 (12.5 mL)
dropwise, and it was allowed to warm to 2208C during
3.5 h with stirring. The reaction was quenched by an
addition of sat. Na2CO3 aq, extracted with ether, dried over
Na2SO4, and then evaporated. The crude product was
purified on preparative silica gel TLC (pre-treated with
phosphate buffer, hexane–ether¼4:1£5) to give the title
compound as a colorless oil. Yield 211.9 mg (6.6 mmol,
87%).
1H NMR (270 MHz, CDCl3) d 0.95 (t, 3H, J¼7.1 Hz), 1.19
(t, 3H, J¼7.4 Hz), 1.23–1.90 (m, 9H), 2.42 (s, 3H), 3.25
(brs, 1H), 3.49–3.92 (m, 3H), 5.12 (d, 1H, J¼7.4 Hz), 7.29
(d, 2H, J¼8.1 Hz), 7.67 (d, 2H, J¼8.1 Hz); IR (CHCl3)
3500, 2950, 2860, 1340, 1160, 1000 cm21); MS (exact mass
calcd for C17H27NO4S, m/e 341.1661, found m/e 341.1900).
5.4.4. Dithiocarbonic acid O-[6-ethoxy-2-propyl-1-(tolu-
ene-4-sulfonyl)piperidin-3-yl]ester S-methyl ester. To a
stirred solution of NaH (337 mg, 9.84 mmol, 60% oil
dispersion) in THF was added a solution of 6-ethoxy-2-
1H NMR (270 MHz, CDCl3) d 0.93 (t, 3H, J¼7.3 Hz),
1.10–1.77 (m, 10H), 2.33–2.54 (m, 2H), 2.41 (s, 3H),
3.93–4.02 (m, 2H), 5.03–5.09 (m, 2H), 5.72–5.85 (m, 1H),
7.27 (d, 2H, J¼8.1 Hz), 7.71 (d, 2H, J¼8.1 Hz); IR (neat)
propyl-1-(toluene-4-sulfonyl)piperidin-3-ol
(560 mg,
1.64 mmol) in THF (40 mL), and the mixture was refluxed
for 1.5 h. After cooling to 08C, carbondisulfide (0.49 mL,
8.2 mmol) was added to the reaction mixture, which was
refluxed for 0.5 h. Methyl iodide (0.53 mL, 8.5 mmol) was
added dropwise to the resulting reaction mixture at 08C, and
it was refluxed for 0.5 h. The reaction was quenched by an
addition of sat. NaCl aq at 08C, extracted with AcOEt, dried
over Na2SO4, and evaporated. The crude product was
passed through a short silica gel column chromatography
(hexane–ether¼4:1) to give the title dithiocarbonate as a
pale yellow oil. Yield 691 mg (1.6 mmol, 98%). This
material was uded for the next step without further
purification.
2950, 2870, 1640, 1600, 1450, 1330, 1160, 660 cm21
;
[a]2D3¼27.5 (c 0.16, AcOEt); MS (exact mass calcd for
C18H27NO2S, m/e 321.1762, found m/e 321.2300).
5.4.7. 2-Hex-2-enyl-6-propyl-1-(toluene-4-sulfonyl)-
piperidine (13). Ozone was bubbled into a solution of 2-
allyl-6-propyl-1-(toluene-4-sulfonyl)piperidine (100 mg,
0.31 mmol) in CH2Cl2 (8 mL) at 2788C until the starting
material was consumed. The reaction was quenched by an
addition of dimethylsulfide (0.057 mL, 0.78 mmol), and
then warmed to room temperature. The resulting mixture
was evaporated in vacuo to remove the excess dimethyl-
sulfide.
[6-Propyl-1-(toluene-4-sulfonyl)piperidin-2-yl]-
1H NMR (270 MHz, CDCl3) d 0.95 (t, 3H, J¼5.8 Hz), 1.20
(t, 3H, J¼7.1 Hz), 1.34–2.19 (m, 8H), 2.42 (s, 3H), 2.54 (s,
3H), 3.54–3.60 (m, 1H), 3.83–3.89 (m, 1H), 4.38–4.42 (m,
1H), 5.02–5.11 (m, 1H), 5.15 (d, 1H, J¼3.3 Hz), 7.31 (d,
2H, J¼8.3 Hz), 7.76 (d, 2H, J¼8.3 Hz); IR (CHCl3) 2950,
1340, 1200, 1160, 1060, 960, 750 cm21. Despite several
attempts, a satisfactory mass spectral analysis data could not
acetaldehyde was obtained as a crude product (136 mg),
and used for the next reaction without further purification.
To a suspension of pentyltriphenylphosphonium bromide
(384 mg, 0.93 mmol) in Et2O (4 mL) was added n-butyl
lithium (1.52N, 0.61 mL) dropwise, and the whole was
refluxed for 2 h. To the resulting mixture was added a
solution of the aldehyde in Et2O (4 mL) at 08C, and the